POS0165 DETERMINATION OF DISTINCT PHENOTYPES OF PRIMARY SJÖGREN’S DISEASE USING CLUSTER ANALYSIS BASED ON CLINICAL AND BIOLOGICAL MANIFESTATIONS: DATA FROM 458 PATIENTS FROM THE PARIS SACLAY SJÖGREN’S SYNDROME COHORT
Authors: Y. Nguyen, G. Nocturne, F. Desmoulins, J. Henry, R. Belkhir, E. Bergé, X. Mariette, R. Seror
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, with heterogenous manifestations. Main symptoms included dryness features due to the exocrinopathy, fatigue, and joint pain. In addition, systemic manifestations occur in approximately 30 to 40% of the patients with pSS. Previous attempts made to determine distinct pSS phenotypes used only symptom-based classifications, neglecting the B-cell biological activity and the systemic manifestations, which are clearly linked with disease prognosis. <h3>Objectives</h3> We aimed to identify distinct phenotypes among pSS patients, based on all disease features, including symptoms, systemic manifestations, and biological features, using a non-supervised hierarchical cluster analysis. <h3>Methods</h3> We included pSS patients enrolled in the prospective French Paris-Saclay cohort, if satisfying the ACR/EULAR criteria. We performed an unsupervised multiple correspondence analysis using 26 selected variables to widely cover pSS manifestations: VAS for pain, fatigue, ocular and oral dryness; systemic manifestations as defined by ESSDAI domains; biological parameters such as rheumatoid factor (RF), anti-SSA, -SSB, -RNP, -centromere, -DNA antibodies, high IgG levels, monoclonal component, cryoglobulinemia, low C4 levels; and abnormal Schirmer's test and presence of focal sialadenitis. The first axes were then considered to perform hierarchical clustering based on the Ward method. The number of clusters was determined visually on the plotted dendrogram and with the gain in inertia. <h3>Results</h3> We included 458 pSS patients in the analyses (95% women, median age 49 yrs). Cluster hierarchical classification yield in three homogenous groups of patients. 1. Cluster 1 (n=121) included patients with high symptom burden (median [IQR] ESSPRI 6.6 [5.6–7.7]), but low systemic activity (ESSDAI 1; [0-2]) 2. Cluster 2 (n=110) included a higher proportion of men (15%) and of patients from African ancestry (19%), with high level of dryness (overall dryness VAS 66 [46–81]) and fatigue (VAS 70 [45–84] but low level of pain (pain VAS 53 [20–77]; high systemic activity (ESSDAI 5 [2–8]): lymphadenopathy (11%), cutaneous (7%), pulmonary (12%), PNS (11%), and articular (40%) involvements; frequent other auto-antibodies: anti-RNP (9.2%), anti-centromere (12%), anti-DNA (16%) and cryoglobulinemia (3.5%). 3. Cluster 3 (n=195) included younger patients (median age 44 yrs), with low symptom burden (ESSPRI 4.9 [3.3–6.2]), low systemic activity (ESSDAI 2 [1–4]), but with frequent B-cell activation signs: biological ESSDAI domain (58%), high IgG levels (52%), rheumatoid factors (58%), low C4 levels (22%); and higher rates of anti-SSA (86%) and -SSB (46%) antibodies. Patients with history of lymphoma were identified in cluster 2 (n=8, 5.6%) and 3 (n=7, 3.6%). <h3>Conclusion</h3> Using an unsupervised clustering method, and including parameter that encompass all disease features, we identified three distinct subgroups of pSS patients that were 1/ high symptom burden without systemic features; 2/ Systemic features 3/ B-cell biologically active with low-symptom burden. Our study highlights the underlying idea of heterogeneous pathophysiological mechanisms and could help further stratifications among pSS patients. Further studies are needed to assess whether disease evolution is different across these subgroups. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.